SEATTLE--Fludarabine (Fludara) has demonstrated impressive results
in previously untreated patients with active chronic lymphocytic
leukemia (CLL) when compared with chlorambucil (Leukeran), Kanti
Rai, MD, said at the American Society of Hematology (ASH) annual
"Chlorambucil has been the gold standard treatment for CLL,"
said Dr. Rai, chief of the Department of Hematology and Oncology,
Long Island Jewish Hospital, New Hyde Park, NY. Although chlorambucil
produces response rates of up to 60% to 70%, the great majority
are partial, not complete, responses. "Overall, the natural
history of CLL has not been shown to be altered or improved by
any treatment, and nothing we did was improving survival,"
Fludarabine is currently indicated for the treatment of patients
with B-cell CLL who have not responded to, or whose disease has
progressed during, treatment with a regimen containing at least
one standard alkylating agent. A study from M.D. Anderson showed
that fludarabine was significantly more effective in previously
untreated patients with active disease, compared with other drugs.
This finding prompted the randomized intergroup study in previously
untreated CLL patients with active disease, Dr. Rai said. The
study involved the Cancer and Leukemia Group B (CALGB), Southwest
Oncology Group (SWOG), National Cancer Institute (NCI), Clinical
Trial Group of the NCI of Canada, and the Eastern Cooperative
Oncology Group (ECOG).
Over a period of 3½ years (October 1990 through April 1994),
more than 450 intermediate-risk and high-risk patients were randomized
to receive either flu-darabine, 25 mg/m² by ½-hour intravenous
infusion daily from days 1 to 5 every 4 weeks, or chlorambucil,
40 mg/m² by mouth on day 1 every 4 weeks.
Initially, a third randomized arm combined the two drugs but was
closed when an interim analysis showed unacceptably high hematologic
toxicity and a response rate no better than that achieved by fludarabine
alone, Dr. Rai said.
The study, with a primary endpoint of complete remission, was
comprised of two phases: Patients showing continued beneficial
response received the assigned therapy for a maximum of 12 months,
and nonresponding patients and those relapsing within 6 months
were crossed over to the alternate therapy.